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| 6. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 9. |
- Daniel, M., et al.
(författare)
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Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries
- 2018
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 131:9, s. 1118-1124
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease. (C) 2018 Elsevier Inc. All rights reserved.
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| 10. |
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| 11. |
- Graham, Jesse R., et al.
(författare)
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The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline
- 2016
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Ingår i: Journal of Experimental Social Psychology. - : Elsevier. - 1096-0465 .- 0022-1031. ; 66, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.
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| 12. |
- Guath, Mona, et al.
(författare)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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| 13. |
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| 14. |
- Washburn, Anthony N., et al.
(författare)
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Data from a pre-publication independent replication initiative examining ten moral judgement effects
- 2016
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Ingår i: Scientific Data. - : Nature Research (part of Springer Nature): Fully open access journals / Nature Publishing Group. - 2052-4463. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires.
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| 15. |
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| 16. |
- Agewall, S, et al.
(författare)
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Risk factors for myocardial infarction with normal coronary arteries and myocarditis compared with myocardial infarction with coronary artery stenosis
- 2012
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Ingår i: Angiology. - : SAGE Publications. - 1940-1574 .- 0003-3197. ; 63:7, s. 500-503
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Tidskriftsartikel (refereegranskat)abstract
- The interest and awareness of myocardial infarction with normal coronary arteries (MINCA) have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy, and new sensitive troponin analyses. The prevalence of MINCA in all patients with myocardial infarction (MI) was registered during a 3-month period in the Stockholm metropolitan area in Sweden. The results showed that MINCA is more common than previously thought (7%) and affecting one third of every woman with MI. Patients with myocarditis were younger and more often presented with signs of inflammation such as elevated C-reactive protein and fever. Myocarditis constitutes an important differential diagnosis for coronary artery disease. There is a need for larger studies of MINCA, including investigation with cardiac magnetic resonance imaging, to establish prevalence and pathological process in this important subgroup of MI.
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| 17. |
- Andersson, David C., et al.
(författare)
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Changes in dynamics of alpha-chymotrypsin due to covalent inhibitors investigated by elastic incoherent neutron scattering
- 2017
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : ROYAL SOC CHEMISTRY. - 1463-9076 .- 1463-9084. ; 19:37, s. 25369-25379
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Tidskriftsartikel (refereegranskat)abstract
- An essential role of enzymes is to catalyze various chemical reactions in the human body and inhibition of the enzymatic activity by small molecules is the mechanism of action of many drugs or tool compounds used to study biological processes. Here, we investigate the effect on the dynamics of the serine protease alpha-chymotrypsin when in complex with two different covalently bound inhibitors using elastic incoherent neutron scattering. The results show that the inhibited enzyme displays enhanced dynamics compared to the free form. The difference was prominent at higher temperatures (240-310 K) and the type of motions that differ include both small amplitude motions, such as hydrogen atom rotations around a methyl group, and large amplitude motions, such as amino acid side chain movements. The measurements were analyzed with multivariate methods in addition to the standard univariate methods, allowing for a more in-depth analysis of the types of motions that differ between the two forms. The binding strength of an inhibitor is linked to the changes in dynamics occurring during the inhibitor-enzyme binding event and thus these results may aid in the deconvolution of this fundamental event and in the design of new inhibitors.
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| 19. |
- Björkstrand, Johannes, et al.
(författare)
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Evaluating an internet-delivered fear conditioning and extinction protocol using response times and affective ratings
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Pavlovian fear conditioning is widely used to study mechanisms of fear learning, but high-throughput studies are hampered by the labor-intensive nature of examining participants in the lab. To circumvent this bottle-neck, fear conditioning tasks have been developed for remote delivery. Previous studies have examined remotely delivered fear conditioning protocols using expectancy and affective ratings. Here we replicate and extend these findings using an internet-delivered version of the Screaming Lady paradigm, evaluating the effects on negative affective ratings and response time to an auditory probe during stimulus presentation. In a sample of 80 adults, we observed clear evidence of both fear acquisition and extinction using affective ratings. Response times were faster when probed early, but not later, during presentation of stimuli paired with an aversive scream. The response time findings are at odds with previous lab-based studies showing slower as opposed to faster responses to threat-predicting cues. The findings underscore the feasibility of employing remotely delivered fear conditioning paradigms with affective ratings as outcome. Findings further highlight the need for research examining optimal parameters for concurrent response time measures or alternate non-verbal indicators of conditioned responses in Pavlovian conditioning protocols.
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| 20. |
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| 21. |
- Collste, O., et al.
(författare)
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Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study
- 2013
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 273:2, s. 189-196
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Tidskriftsartikel (refereegranskat)abstract
- Collste O, Sorensson P, Frick M, Agewall S, Daniel M, Henareh L, Ekenback C, Eurenius L, Guiron C, Jernberg T, Hofman-Bang C, Malmqvist K, Nagy E, Arheden H, Tornvall P (Sodersjukhuset, Stockholm; Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; University of Oslo, Oslo, Norway; Sankt Goran Hospital Capio, Karolinska Institutet, Stockholm; Huddinge, Stockholm; Danderyd Hospital, Karolinska Institutet, Stockholm; and Skane University Hospital, Lund University, Lund, Sweden). Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study. J Intern Med 2013; 273: 189-196. Objectives Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. Design The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. Setting Coronary care units in the Stockholm metropolitan area. Subjects Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. Results In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 628) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. Conclusion In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.
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| 22. |
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| 23. |
- Dinkla, Katrin, et al.
(författare)
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Identification of a streptococcal octapeptide motif involved in acute rheumatic fever
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:26, s. 18686-18693
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Tidskriftsartikel (refereegranskat)abstract
- Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by certain group A streptococci. One mechanism applied by streptococcal strains capable of causing acute rheumatic fever is formation of an autoantigenic complex with human collagen IV. In some geographic regions with a high incidence of acute rheumatic fever pharyngeal carriage of group C and group G streptococci prevails. Examination of such strains revealed the presence of M-like surface proteins that bind human collagen. Using a peptide array and recombinant proteins with targeted amino acid substitutions, we could demonstrate that formation of collagen complexes during streptococcal infections depends on an octapeptide motif, which is present in collagen binding M and M-like proteins of different beta-hemolytic streptococcal species. Mice immunized with streptococcal proteins that contain the collagen binding octapeptide motif developed high serum titers of anti-collagen antibodies. In sera of rheumatic fever patients such a collagen autoimmune response was accompanied by specific reactivity against the collagen-binding proteins, linking the observed effect to clinical cases. Taken together, the data demonstrate that the identified octapeptide motif through its action on collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication of streptococci that express proteins with the collagen binding motif appears advisable for controlling rheumatic fever.
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| 24. |
- Frick, F, et al.
(författare)
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Interaction between growth hormone and insulin in the regulation of lipoprotein metabolism in the rat
- 2002
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 283:5, s. E1023-E1031
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Tidskriftsartikel (refereegranskat)abstract
- The importance of insulin for the in vivo effects of growth hormone (GH) on lipid and lipoprotein metabolism was investigated by examining the effects of GH treatment of hypophysectomized (Hx) female rats with and without concomitant insulin treatment. Hypophysectomy-induced changes of HDL, apolipoprotein (apo)E, LDL, and apoB levels were normalized by GH treatment but not affected by insulin treatment. The hepatic triglyceride secretion rate was lower in Hx rats than in normal rats and increased by GH treatment. This effect of GH was blunted by insulin treatment. The triglyceride content in the liver changed in parallel with the changes in triglyceride secretion rate, indicating that the effect of the hormones on triglyceride secretion was dependent on changed availability of triglycerides for VLDL assembly. GH and insulin independently increased editing of apoB mRNA, but the effects were not additive. The expression of fatty-acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and sterol regulatory element-binding protein-1c (SREBP-1c) was increased by GH treatment. Insulin and GH had no additive effects on these genes; instead, insulin blunted the effect of GH on SREBP-1c mRNA. In contrast to the liver, adipose tissue expression of SREBP-1c, FAS, or SCD-1 mRNA was not influenced by GH. In conclusion, the increased hepatic expression of lipogenic enzymes after GH treatment may be explained by increased expression of SREBP-1c. Insulin does not mediate the effects of GH but inhibits the stimulatory effect of GH on hepatic SREBP-1c expression and triglyceride secretion rate.
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| 25. |
- Frick, Inga-Maria, et al.
(författare)
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Convergent evolution among immunoglobulin G-binding bacterial proteins
- 1992
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Ingår i: Proceedings of the National Academy of Sciences. - 1091-6490. ; 89:18, s. 8532-8536
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Tidskriftsartikel (refereegranskat)abstract
- Protein G, a bacterial cell-wall protein with high affinity for the constant region of IgG (IgGFc) antibodies, contains homologous repeats responsible for the interaction with IgGFc. A synthetic peptide corresponding to an 11-amino acid-long sequence in the COOH-terminal region of the repeats was found to bind to IgGFc and block the interaction with protein G. Moreover, two other IgGFc-binding bacterial proteins (proteins A and H), which do not contain any sequences homologous to the peptide, were also inhibited in their interactions with IgGFc by the peptide. Finally, a decapeptide based on a sequence in IgGFc blocked the binding of all three proteins to IgGFc. This unusually clear example of convergent evolution emphasizes the complexity of protein-protein interactions and suggests that bacterial surface-protein interaction with host protein adds selective advantages to the microorganism.
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| 26. |
- Frick, Julia S, et al.
(författare)
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Identification of commensal bacterial strains that modulate Yersinia enterocolitica and dextran sodium sulfate-induced inflammatory responses : implications for the development of probiotics.
- 2007
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 75:7, s. 3490-7
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Tidskriftsartikel (refereegranskat)abstract
- An increasing body of evidence suggests that probiotic bacteria are effective in the treatment of enteric infections, although the molecular basis of this activity remains elusive. To identify putative probiotics, we tested commensal bacteria in terms of their toxicity, invasiveness, inhibition of Yersinia-induced inflammation in vitro and in vivo, and modulation of dextran sodium sulfate (DSS)-induced colitis in mice. The commensal bacteria Escherichia coli, Bifidobacterium adolescentis, Bacteroides vulgatus, Bacteroides distasonis, and Streptococcus salivarius were screened for adhesion to, invasion of, and toxicity for host epithelial cells (EC), and the strains were tested for their ability to inhibit Y. enterocolitica-induced NF-kappaB activation. Additionally, B. adolescentis was administered to mice orally infected with Y. enterocolitica and to mice with mucosae impaired by DSS treatment. None of the commensal bacteria tested was toxic for or invaded the EC. B. adolescentis, B. distasonis, B. vulgatus, and S. salivarius inhibited the Y. enterocolitica-induced NF-kappaB activation and interleukin-8 production in EC. In line with these findings, B. adolescentis-fed mice had significantly lower results for mean pathogen burden in the visceral organs, intestinal tumor necrosis factor alpha mRNA expression, and loss of body weight upon oral infection with Y. enterocolitica. In addition, the administration of B. adolescentis decelerated inflammation upon DSS treatment in mice. We suggest that our approach might help to identify new probiotics to be used for the treatment of inflammatory and infectious gastrointestinal disorders.
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| 27. |
- Frick, Matilda A, 1979-
(författare)
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Self-Regulation in Childhood : Developmental Mechanisms and Relations to ADHD Symptoms
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Self-regulation is a multi-faceted construct that concerns goal-directed behaviors, which aid individuals in everyday life and in achieving long-term goals. Self-regulation in believed to progress in a hierarchical fashion, in that simple cognitive functions are integrated into more complex functions across development. Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous childhood-onset disorder, characterized by deficits in various aspects of self-regulation, including core symptoms of inattention and hyperactivity/impulsivity, and comorbidity with externalizing disorders such as oppositional defiant disorder (ODD). The last decade has seen a shift from simple etiological models towards more complex ones, which stress multiple pathways to the disorder. In addition, there is an ongoing search for early markers of the condition, which will increase our understanding, enable early detection, intervention, and perhaps even prevention of the full disorder. Cognitive regulation, aspects of temperament (i.e. negative affect, surgency, and effortful control), and parenting are three areas of importance for self-regulation in general and of ADHD symptoms in particular. Grounded in these three constructs, informed by the hierarchical model of self-regulation development, and a multiple pathway perspective on ADHD, the present thesis aimed to map development of self-regulation, with a special focus on inattention and hyperactivity/impulsivity. Four studies were conducted based on three samples, ranging from infancy to 12 years, including both typically developing children and children diagnosed with ADHD. Study I found that early sustained attention predicted later cognitive regulation, providing support for the hierarchical model of self-regulation development. In addition, maternal sensitivity contributed to higher levels of emotion regulation whereas surgency contributed to lower levels of emotion regulation. Study II gained support for a multiple pathway perspective on ADHD, in that higher temperamental regulation and maternal sensitivity contributed to lower levels of inattention and hyperactivity/impulsivity, and higher surgency contributed to higher levels of hyperactivity/impulsivity. Study III replicated findings from Study II and confirmed early temperament markers of later inattention and hyperactivity/impulsivity, and that early cognitive regulation was a poor predictor of later symptoms. Study IV proposed contributions of multiple regulatory functions to ADHD symptoms and elevated negative affect in ODD. The latter was moderated by parental support, which seemed to be a protective factor for children with high levels of negative affect. In all, the findings point to the importance of both intrinsic and extrinsic factors in the development of self-regulation, which seems to progress in a hierarchical fashion. Aspects of temperament rather than cognitive regulation seem to be valid early markers of later inattention and hyperactivity/impulsivity. Multiple pathways to ADHD symptoms are proposed, with contributions of maternal sensitivity and temperament early in development and different regulatory functions in school-aged children. In addition, elevated negative affect in combination with low parental support seem to be characteristic of ODD rather than of core symptoms of ADHD. The thesis contributes to the complexity and heterogeneity of ADHD and that ADHD is best viewed as a developmental disorder, in that the influence of various regulatory factors change over time.
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| 32. |
- Lageman, B, et al.
(författare)
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Kultur der Selbständigkeit
- 1999
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Ingår i: Existenzgründungen und dynamische Wirtschaftsentwicklung. - Berlin : Duncker & Humblot. - 3428096576 ; , s. 61-93
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 33. |
- Lethagen, Stefan, et al.
(författare)
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Effect kinetics of desmopressin-induced platelet retention in healthy volunteers treated with aspirin or placebo
- 2000
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 6:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16-27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery.
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| 34. |
- Markoulli, Maria, et al.
(författare)
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BCLA CLEAR Presbyopia : Epidemiology and impact
- 2024
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Ingår i: Contact lens & anterior eye. - : Elsevier. - 1367-0484 .- 1476-5411.
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Tidskriftsartikel (refereegranskat)abstract
- The global all-ages prevalence of epidemiologically-measured 'functional' presbyopia was estimated at 24.9% in 2015, affecting 1.8 billion people. This prevalence was projected to stabilise at 24.1% in 2030 due to increasing myopia, but to affect more people (2.1 billion) due to population dynamics. Factors affecting the prevalence of presbyopia include age, geographic location, urban versus rural location, sex, and, to a lesser extent, socioeconomic status, literacy and education, health literacy and inequality. Risk factors for early onset of presbyopia included environmental factors, nutrition, near demands, refractive error, accommodative dysfunction, medications, certain health conditions and sleep. Presbyopia was found to impact on quality-of-life, in particular quality of vision, labour force participation, work productivity and financial burden, mental health, social wellbeing and physical health. Current understanding makes it clear that presbyopia is a very common age-related condition that has significant impacts on both patient-reported outcome measures and economics. However, there are complexities in defining presbyopia for epidemiological and impact studies. Standardisation of definitions will assist future synthesis, pattern analysis and sense-making between studies.
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| 35. |
- Mylonas, E, et al.
(författare)
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Single-cell analysis based dissection of clonality in myelofibrosis
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events.
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| 36. |
- Månsson, Kristoffer N T, et al.
(författare)
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Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
- 2015
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual’s long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52%(12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
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| 37. |
- Månsson, Kristoffer, et al.
(författare)
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Predicting Long-Term Outcome of Cognitive Behaviour Therapy for Social Anxiety Disorder Using fMRI and Support Vector Machiness
- 2014
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Ingår i: Abstracts from the 44th Congress of the European Association for Behavioural & Cognitive Therapies.
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Konferensbidrag (refereegranskat)abstract
- Background: Cognitive behavioural therapy (CBT) has yielded robust treatment effects for social anxiety disorder (SAD) but still many patients do not respond fully to treatment, and a substantial proportion relapse after treatment has ended. Identification of robust predictors of sustained treatment responses could be of high clinical importance.Methods: We used functional magnetic resonance imaging (fMRI; 3T General Electric) to assess 26 patients (85% women, mean age 32.3 years) with SAD. Blood-oxygen-level dependent (BOLD) responses to self-referential criticism, i.e. reading sentences such as "Nobody likes you" were compared to criticism referring to other individuals. Responses in the fear network, i.e. the amygdala, hippocampus, anterior cingulate cortex (ACC), and insula, were evaluated in a Support Vector Machine (SVM) approach to predict treatment outcome one-year after Internet-delivered CBT. We applied leave-one-out cross-validation to increase the generalizability of the data.Results: At one-year follow-up, three patients had dropped out. Twelve (52%) of the assessed patients met the response criteria, i.e. very much or much improved according to the Clinical Global Impression-Improvement scale (CGI-I). SVM on initial BOLD response, accurately classified patients according to responder status, based on multi-voxel patterns in the ACC (balanced accuracy of 91.7%, p=.001), and the ACC together with the amygdala (83.0%, p=.004) as well as the hippocampus (73.9%,p=.032).Conclusions: We demonstrate that initial multi-voxel BOLD response patterns to self-referential criticism in the ACC, amygdala, and hippocampus are highly predictive of long-term improvement of CBT in patients with SAD.
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| 38. |
- Nitsche-Schmitz, D. Patric, et al.
(författare)
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Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:24, s. 17530-17536
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Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G ( GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG ( group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pM. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections.
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| 39. |
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| 40. |
- Persson, Anders I., 1973, et al.
(författare)
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Expression of delta opioid receptor mRNA and protein in the rat cerebral cortex and cerebellum is decreased by growth hormone.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 496-503
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Tidskriftsartikel (refereegranskat)abstract
- Hormones released from the pituitary have been shown to regulate the expression of different proteins in the central nervous system. We wanted to examine whether peripheral administration of bovine growth hormone (bGH) regulates the expression of delta-opioid receptor (DOR) in the cerebral cortex and cerebellum. Expression of the DOR protein was quantified using Western blot densitometry. DOR mRNA was quantified with a solution hybridization RNase protection assay. Hypophysectomized (Hx) and untreated normal female rats were included in the study. All Hx rats were hormonally treated with cortisol (400 microg/kg/day) and L-thyroxine (10 microg/kg/day) for 19 days. Hypophysectomy resulted in a threefold increase in cerebral cortex and a twofold increase in cerebellum of the DOR protein compared with normal rats. One subgroup of Hx rats received bGH (1 mg/kg body weight) as a daily subcutaneous injection for 19 days. This treatment normalized the levels of DOR protein in the cerebral cortex and cerebellum. Immunohistochemical experiments showed that GH decreased DOR expression especially in layers II-VI in cerebral cortex and in stratum moleculare in cerebellum. Quantification of DOR mRNA by solution hybridization RNase protection assay corresponded to the DOR protein measurements. We conclude that the expression of DORs in cerebral cortex and cerebellum is regulated by GH.
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| 41. |
- Santarius, T., et al.
(författare)
-
Digital sufficiency : conceptual considerations for ICTs on a finite planet
- 2022
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Ingår i: Annales des télécommunications. - : Springer Nature. - 0003-4347 .- 1958-9395.
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Tidskriftsartikel (refereegranskat)abstract
- ICT hold significant potential to increase resource and energy efficiencies and contribute to a circular economy. Yet unresolved is whether the aggregated net effect of ICT overall mitigates or aggravates environmental burdens. While the savings potentials have been explored, drivers that prevent these and possible counter measures have not been researched thoroughly. The concept digital sufficiency constitutes a basis to understand how ICT can become part of the essential environmental transformation. Digital sufficiency consists of four dimensions, each suggesting a set of strategies and policy proposals: (a) hardware sufficiency, which aims for fewer devices needing to be produced and their absolute energy demand being kept to the lowest level possible to perform the desired tasks; (b) software sufficiency, which covers ensuring that data traffic and hardware utilization during application are kept as low as possible; (c) user sufficiency, which strives for users applying digital devices frugally and using ICT in a way that promotes sustainable lifestyles; and (d) economic sufficiency, which aspires to digitalization supporting a transition to an economy characterized not by economic growth as the primary goal but by sufficient production and consumption within planetary boundaries. The policies for hardware and software sufficiency are relatively easily conceivable and executable. Policies for user and economic sufficiency are politically more difficult to implement and relate strongly to policies for environmental transformation in general. This article argues for comprehensive policies for digital sufficiency, which are indispensible if ICT are to play a beneficial role in overall environmental transformation.
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| 42. |
- Åkerlind, Ingemar, et al.
(författare)
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Health and work organization
- 2007
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Ingår i: Work Health and Management Control. - : Thomson Fakta, Stockholm. - 9789176102725 ; , s. 77-95
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Bokkapitel (refereegranskat)abstract
- In WHP, there is a need for an organizational approach, as has already been mandated in preventive OHS management. This approach calls for changes in organizational systems that improve an individual’s chance of becoming healthy. The aim is that health becomes an essential issue in the corporate strategy and policy as well as the management control system of the company. WHP ought to be an intrinsic and central part of the organizational system rather than something that is forced through legislation or is the subject of occasional programmes offered to the employees. Health must be considered in its broadest sense, with the realization that the essential parts of organizational workplace health are complex and broad-reaching. However, to accomplish this goal, many of the problems that hinder the recognition of health as a company resource have to be resolved. Our book aims to contribute to this resolution.
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